CAREER: Modeling and Decoding Host-Microbiome Interactions in Gingival Tissue

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The human body houses many different, but connected, microbial populations. For example, populations of tiny living things like bacteria, viruses and fungi, that can’t be seen with the naked eye. Some microbes make us sick while others are important for our health. Their balance or imbalance with each other and the surrounding tissues can exert long-lasting and wide-ranging effects on an individual’s state of health or disease. Of particular interest is the microbiota in the oral cavity, as it serves as a potential reservoir for pathogenic (disease causing) bacteria. However, very little is known about the relationship of various diseases and the oral microbiome. The research goal of this CAREER project is to understand the connection between the human oral tissue, the oral microbiome, and how they interact. This will be accomplished by creating an in vitro (in the lab) model of the human gingival (gum) tissue system capable of studying diverse microbial populations and their connection to overall human health. The goal of the project’s educational plan, called ResAx, is to provide a working model to address the drop in enrollment in low resources academic institutions that could be transposed to other research areas (i.e., medical devices, protein engineering). The multidisciplinary research project will provide opportunities to expand research access and education to undergraduate students enrolled in the BME curriculum at University of Massachusetts Lowell and to support a paid Summer Training Program for rising junior high school students in the local Lowell community. ResAx aims to provide equitable access to high-quality education experiences to more than 5,000 underserved students.This CAREER project targets the development of an in vitro gingival tissue system to study the role of microbial communities on human oral health and disease, with potential repercussion on diverse pathologies such as periodontitis, atopic dermatitis, asthma, and inflammatory bowel disease. In addition to representing a large population and economic market, these chronic diseases are emergent drivers of global socioeconomic status. The vision of this CAREER project will be accomplished by: (i) the development and validation of a microphysiological system to study oral host-pathogens interactions and microbiome biogeography under different clinical conditions (healthy, gingivitis and periodontitis); (ii) the engineering of an inflamed gingivitis model based on human primary neutrophils to identify a clinical fingerprint for early dysbiosis presentation; and (iii) a periodontitis model based on activated B and T lymphocytes and clinically driven tissue characteristics to investigate the effect of lipid mediators on inflammation resolution and induced changes on the established polymicrobial community.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.